2. Academic Validation
  3. Unveiling the binding mode of perfluorooctanoic acid to human serum albumin

Unveiling the binding mode of perfluorooctanoic acid to human serum albumin

  • Protein Sci. 2021 Apr;30(4):830-841. doi: 10.1002/pro.4036.
Lorenzo Maso 1,  Matteo Trande 2,  Stefano Liberi 2,  Giulia Moro 2 3,  Elise Daems 3 4,  Sara Linciano 2,  Frank Sobott 4 5,  Sonia Covaceuszach 6,  Alberto Cassetta 6,  Silvano Fasolato 7,  Ligia M Moretto 2,  Karolien De Wael 3,  Laura Cendron 1,  Alessandro Angelini 2 8
Affiliations

Affiliations

  • 1 Department of Biology, University of Padua, Padova, Italy.
  • 2 Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, Mestre, Italy.
  • 3 Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium.
  • 4 Department of Chemistry, University of Antwerp, Antwerp, Belgium.
  • 5 Astbury Centre for Structural Molecular Biology and School of Molecular and Cellular Biology, University of Leeds, Leeds, UK.
  • 6 Istituto di Cristallografia - CNR, Trieste Outstation, Trieste, Italy.
  • 7 Department of Medicine, University of Padua, Padova, Italy.
  • 8 European Centre for Living Technology (ECLT), Venice, Italy.
PMID: 33550662 DOI: 10.1002/pro.4036
Abstract

Perfluorooctanoic acid (PFOA) is a toxic compound that is absorbed and distributed throughout the body by noncovalent binding to serum proteins such as human serum albumin (hSA). Though the interaction between PFOA and hSA has been already assessed using various analytical techniques, a high resolution and detailed analysis of the binding mode is still lacking. We report here the crystal structure of hSA in complex with PFOA and a medium-chain saturated fatty acid (FA). A total of eight distinct binding sites, four occupied by PFOAs and four by FAs, have been identified. In solution binding studies confirmed the 4:1 PFOA-hSA stoichiometry and revealed the presence of one high and three low affinity binding sites. Competition experiments with known hSA-binding drugs allowed locating the high affinity binding site in sub-domain IIIA. The elucidation of the molecular basis of the interaction between PFOA and hSA might provide not only a better assessment of the absorption and elimination mechanisms of these compounds in vivo but also have implications for the development of novel molecular receptors for diagnostic and biotechnological applications.

Keywords

binding mode; crystal structure; fluoroalkyl substances; human serum albumin; molecular interaction; perfluorooctanoic acid.

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